Antimicrobial compositions containing aluminum halide compounds

ABSTRACT

Antimicrobial compositions in which an inorganic moiety constitutes the major portion of the composition are produced by combining an aluminum halide compound with minor quantities of polyhalocarbanilide and another bactericidal agent selected from the group consisting of halogenated bisphenols and 2,2,4&#39;&#39;trichloro-2&#39;&#39;-hydroxydiphenyl ether. The resulting germicidal compositions exhibit synergistic antimicrobial effects against bacteria and fungi.

United States Patent [1 1 Rubino et al.

[4 Jan. 14, 1975 [54] ANTIMICROBIAL COMPOSITIONS CONTAINING ALUMINUM HALIDE COMPOUNDS [75] Inventors: Andrew M. Rubino, New

Providence; William S. Gilman, South Plainfield; John L. Jones, North Plainfield, all of [73] Assignee: Armour Pharmaceutical Company,

Phoenix, Ariz.

[22] Filed: Nov. 8, 1971 [21] Appl. No.: 196,751

[52] US. Cl 424/157, 424/154, 424/340,

424/347 [51] Int. Cl. A0ln 13/00, A6lk 27/00 [58] Field of Search; 424/157, 154, 340, 347

[56] References Cited UNITED STATES PATENTS 3,177,115 4/1965 Casely et a1. 424/322 OTHER PUBLICATIONS U.S. Dispensatory-25th edit. 1955, page 56.

Primary Examiner-Sam Rosen Attorney, Agent, or Firm-Frank T. Barber; Carl C. Batz [57] ABSTRACT 16 Claims, No Drawings ANTIMICROBIAL COMPOSITIONS CONTAINING ALUMINUM HALIDE COMPOUNDS The present invention relates to germicidal compositions exhibiting synergistic antimicrobial effects against bacteria and fungi. More particularly, it relates to the production and use of a novel tri-component composition of matter consisting essentially of (i) an aluminum halide compound, (ii) a polyhalocarbanilide and (iii) a bactericidal agent selected from the group consisting of halogenated bisphenols and 2,4,4'-trichloro-2'- hydroxydiphenyl ether. It has now been found that this system exhibits a high degree of broad spectrum antimicrobial activity and furthermore, that it exhibits a synergistic effect against both bacteria and fungi. More specifically, it has been found that the antimicrobial effect derived from this tri-component system exceeds the sum of the antimicrobial effects derivable from each component taken individually.

Heretofore, each of the individual components of the novel tri-component system of the present invention has been recognized as having antimicrobial properties. In the case of basic aluminum halides, some low level bactericidal and bacteriostatic characteristics have been reported. The utilization of halogenated bisphenols in soaps and detergents and for deodorant purposes is well known along with its bactericidal activity against Gram-positive bacteria. The inherent limitations of halogenated bisphenolic compounds, such as high relative toxicity, photosensitivity, reactivity with heavy metal ions, and lack of antimicrobial activity against fungi and Gram-negative bacteria are also well known. In addition, the utilization of 2,4,4'-trichloro- 2'-hydroxydiphenyl ether in topical preparations is well known. However, it has not been shown to be economically competitive with other similar antimicrobial compositions. Halogenated carbanilides are also deficient in their properties or abilities to combat Gram-negative bacteria and fungi at realistic concentrations.

US. Pat. No. 3,177,155 discloses a synergistic combination consisting essentially of a halogenatedbisphenolic compoundmixed with trichlorocarbanilide (TCC) in which the relative range of components is described as 9 to 1 parts by weight of TCC to 9 to 1 parts 3 by weight of the halogenated bisphenolic compound (su'ch'as hexachlorophene). Many of the described difficulties associated with the individual constituents as discussed above, have been corrected by the combination set forth in US. Pat. No. 3,177,155. However, the combination does not exhibit sufficient activity against fungi and the inherent photo-sensitivity, toxicity and reactivity with heavy metal ions which are associated as impurities in dermatological formulation ingredients, continue to be a problem.

Accordingly, it is an object of the present invention to provide new antimicrobial compositions which exhibit broad spectrum antimicrobial activity against Gram-negative and Gram-positive bacteria, resident skin bacteria, dermatophytes, yeasts, and various fungi.

Another object of the present invention is to provide new antimicrobial compositions in which the concentration of the antimicrobial agent, such as a halogenated bisphenol or 2,4,4-trichloro-2'-hydroxydiphenyl ether, is reduced substantially whereby the technical and economic limitations associated with their uses are also reduced substantially.

A further object of the present invention is to provide new antimicrobial compositions containing at least by weight of the inorganic moiety (aluminum halide compound) whereby the inherent astringent and healing characteristics associated with this aluminum salt enhances the topical dermatological usage of the resultant composition.

It is a feature of thepresent invention that the novel antimicrobial compositions produced afford a topically employable dermatological ingredient for creams, lotions, ointments, powders and the like where germicidal activity is required along with astringency and healing characteristics. In addition, it has been found that the antimicrobial activities derivable from this novel composition exceed the antimicrobial components activity of several presently marketed topical products i.e. foot care deodorants, diaper rash, aftershave, minor first aid antiseptics, mouth washes, dandruff treatments, female personal care products, proctological products, and other topical systems, along with detergent, disinfectant, and fabric sanitization products. Thus, various usages become apparent by the obvious improvements derivable by incorporating the'proposed system, instead of existing systems, into the abovementioned products. Furthermore, since the inorganic moiety represents such a large portion of the system, nontopical applications such as in paints, glues, cements, mildewcide applications and as non-foaming microbicides for slime and sludge prevention in wet air cleaning systems are also comtemplated.

Broadly, the present invention provides an antimicrobial composition containing as its essential active ingredients, a synergistic combination of from 70 to 99.5% by weight of an aluminum halide compound, from 0.25 to 20% by weight of a bactericidal agent selected from the group consisting of halogenated bisphenols and 2,4, 4 -trichloro-2'-hydroxydiphenyl ether, 1 and from 0.25 to 20 weight percent of polyhalocarbanilide.

In accordance with the present invention, the aluminum halide compound is a coordinated complex of aluminum which can be represented by the general formula: 1

Aston). Ae where ri is 0 5 and-need not be an integer; where A is chlorine, bromine or iodine ora mixture thereof; and Q is waterand/or a polyhydroxycompound having at least two carbon atoms, each of which is linked to a hydroxy group, and where the total amount of the free and coordinated constituent Q is in the range of from about 15 to 40 percent by weight of the total weight of the complex. Such compounds are referred to herein as hydrated aluminum halide complexes and hydrated or non-hydrated, alcoholated aluminum halide complexes.

BASIC ALUMINUM HALIDE COMPLEXES As used herein, the term aluminum halide complex" refers to compounds such as basic aluminum halides or normal aluminum halides having the general formula:

wherein: 0 y 6 and need not be an integer, and X is a halide selected from the group consisting of chlorine, bromine and iodine and mixtures thereof. Basic aluminum halides contain varying quantities of basic units such as Al (OH) X Al (OH) X and Al (OH),,X and normal aluminum halides. However, because of the infinite number of combinations with Aux, up to pre- 3 cipitation ofAl (OH) y in the above formula can vary in infinitely small values from'0 to 6. In addition, it should be understood that the above formula is greatly simplified and is intended to include basic aluminum halides containing coordinated or bound molecules of water as well as basic aluminum halide polymers, complexes and mixtures of the above.

Particularly suitable for the purposes of the present invention are basic aluminum halides having a basicity in the range of about one-third to five-sixths and the normal aluminum halide salts; that is, compounds of the above general formula having a predominance of units of Al X Al (OH) X AMQHLX and/or .Al (OH) X such that the aluminum to halide mol ratio ranges from about 0.5 to 3.0.

HYDRATED BASIC ALUMINUM HALIDE COMPLEXES As is well known, basic aluminum halide complexes which are hydrated or partially hydrated are produced, for example, by adding aluminum metal to an aluminum halide or a hydrogen halide in water solution and partially drying the product to a solid form short of decomposition to Al(OH) and/or A1 0 Thus, the hydrated basic aluminum halide compounds used in the formation of the antimicrobial compositions of the present invention can be represented by the general formula:

wherein: n, x and y are integers such that x y 3n; A is chlorine, bromine, iodine or mixtures thereof; and X is from 2 to 4 and need not be an integer. Such compounds are substantiallyalcohol insoluble and require the addition of water or other water-containing solvents to obtain a soluble state.

Recent attempts to improve the alcohol solubility of basic aluminumchloride solids have led to the development of alcohol soluble basic aluminumv chlorides which are made by carefully controlling the molar ratio of aluminum to, chloride and theamount of free and co-.

ordinated water'present in the solid. Examples of twothirds to five-sixths basic aluminum chloride solids having a calculated weight percent of free and coordinated water of about 18 to about '20, which are suitable for use in the antimicrobial compositions of this invention, are disclosed in copending application Ser. No. 84,093 for Alcohol Soluble Basic Aluminum Chlorides and Method of Making Same", filed Oct. 26, 1970 by John L. Jon es and Andrew M. Rubino and assigned to the same assignee as the assignee of the present invention.

ALCOHOLATED BASIC ALUMINUM HALIDE COMPLEXES Numerous inorganic-organic coordinated complexes seph N. Slater, Jr.; U.S. Pat. No. 3,520,911 for Method of Making Alcohol-SolubleComplexes of Aluminum issued to John L. Jones and Andrew M. Rubino; and U.S. Pat. No. 3,523,]30 for Method of Making Alcohol-Soluble Complexes of Aluminum, issued to John L. Jones and Andrew M. Rubino. Such compounds can be represented as:

where n, x, y and z are integers such that x y z 3n, R is an alkyl group, A is chloride, bromide or iodide or a mixture of these, and X may be zero to several weight percent of the total compound.

An example of such coordinated complexes of aluminum is the aluminum chlorohydroxide-propylene glycol complex sold under the trademark REHYDROL ASC by the Reheis Chemical Company, Division of Armour Pharmaceutical Company. The solid contains about by weight of aluminum chlorohydroxide having an aluminum to chloride ratio on to 1, and may be considered to be a poly nuclear (Werner type) coordination complex of basic aluminum chloride and propylene glycol in which the water molecules normally coordinated to aluminum in the chlorohydroxide have been displaced by the alcoholic oxygens of the glycol resulting in a relatively less polar complex of low water content.

Substantially anhydrous, i.e. a water content of less than about 2 percent by weight, basic aluminum halide complexes which are alcoholated'with' an aliphatic alcohol having from 1-4 carbon atoms are disclosed in copending application Ser. No. 84,172 for Alcoholated Basic Aluminum Halide Compounds and Methods of Making Same" filed on Oct. 26, 1970 by the present'inventors. Such compounds are represented by the general formula:

MQHMN wherein x, y and nare integers such that x y 3n; ROH is at least one aliphatic alcohol, X is a number such that the total amount of free and coordinated alcohol in the complex is about 10 to 40.weig'ht percent of the complex; and A is chlorine, bromine, iodine or a mixture thereof. f

Preferably, thecoordinated complex of aluminumis an aluminum chlorohydroxy complex corresponding to the formula:

in which X is a halide selected from the group consisting of chlorine, bromine and iodine and mixtures thereof, and n is from 1 to-5. Most preferred is the basic aluminum chloride having the approximate formulation Al (OH) Cl with the atomic ratio of aluminum to chloride being between 1.9 and2.l to l. I

Suitable halogenated bisphenols for use in preparing an antimicrobial composition according to the present invention are unalkylated or alkylated polyhalobisphenols which can be represented according to their chemical structure as follows:

wherein X represents a halogen and need not corre spond to the halogen on the basic aluminum salt, n represents an integer from 1 to 3, and B represents a divalent radical including alkylene radicals and halosubstituted alkylene radicals having from 1 to 4 carbon The third constituent of the antimicrobial composition of the present invention is a polyhalocarbanilide of which the preferred composition is identified as 3,4,4- trichlorocarbanilide (TCC) or its position isomer 3,3',4-trichlorocarbanilide, each of which can be iden- 5 atoms, or a functional group including sulfur; and R in tlfled by the following structural formula: the case of alkylated polyhalobisphenols is an alkyl group having from 1 to 4 carbon atoms. C1 0 The preferred compounds are symmetrical in struc- H 1 tural configuration. Specific examples of the unalk- C1 ylated polyhalobisphenols include 2,2-dihydroxy-3,5,6,3 ',5,6-hexachlorodiphenyl methane, 2,2'-d'h drox -3,5,3' 5-t t hl r d h l thanel y y e rac o 0 ip eny me EXAMPLE I 2,2-dihyd roxy-4,5,4,5 -tetrachlorodiphenyl meth- Antimicrobial compositions exemplary of the present ane, invention are prepared by intimately mixing the con- 2,2-dihydroxy-3,4,3',4-tetrachlorodiphenyl meth- I stituents listed in Table I below, to produce a synergisane, tic admixture by simple dry blending of the three com- 2,2'-dihydroxy-5,5-dibromodiphenyl methane, P

TABLE I 2,4,4'-trichloro- 5/6 Basic Aluminum 3,4.4'-trichloro- 2-hydroxy- No. Chloride Hcxachlorophene carhunilide diphenyl other I 99.5 0.25 0.25 2 99.5 0.25 0.25 3 98 1 I 4 9s l l 5 90 5 5 6 90 5 5 7 85 I0 5 8 85 5 l0 9 s5 10 5 10 85 5 l0 u 80 l0 l0 l2 so 10- l0 I3 89 10 1 14' 75 I5 10 i5 70 I0 16 70 20 l0 I7 70 i 20 I0 I8 70 I0 20 2,'2'-dihydr6iy-3,5,3',5' tetrachlrdiplienyl sulfide, g y, the p du ti n of the triand component system can be carried out by co-dissolution 2,2-dihydroxy-5,5-dichlorodiphenyl sulfide of the components in some mutual solvent such as an- Specific examples of the alkylated halogenated bishydrous ethanfll which y be denatured, and phenols include moving the solvent using either vacuum or heat or vac- 2,2'-dihydroxy-3,3'-dimethyl-5,5'-dichlorodiphenyl uum and heat in combination. Alternatively, the dry lfid product can be recovered by spray drying or freeze dry- 2,2'-dihydroxy-3,3-dimethyl-5,5'-dichlorodiphenyling utilizing conventional drying apparatus. Concentrai hl h tion adjustments of the respective solutes are m ain 2 2'- 1 4 l tained in the finished product in the same ratios orpro- 2,2' th l -bi (6- b t l.4- hl h l) portions as added. When dried from solution, such anti- 2,2'-ethylidene-bis(4-chloro-6-isopropylphe l) microbial compositions are more homogepcousthan 2',2-ethylidene-bis(6-sec-butyl-4-chlorophenol), those produced by simple dry blending and m addition, 2,2-isopropylidene-bis(4-chloro-6- exhibit greater antimicrobial activity. It is believed that isopropylphenol), and a newly developed chemical or physical bond may ac- 2,2'-isopropylidene-bis(6-sec-butyl-4-chlorophenol). count for this increase in activity when dried from alco- A preferred polyhalobisphenol in accordance with Ml Solutioflthe present invention is 2,2'-dihydroxy-3,5,6,3,5,6- A specific example of one particular composition hexachlorodiphenyl methane, commonly referred to as dried from an alcoholic solution is described by the folhexachlorophene. lowing example. A 300 gram sample of spray dried 5/6 2,4,4-trichloro-2'-hydroxy bisphenyl ether which basic aluminum chloride described in copending applican be utilized in place of the halogenated bisphenol is cation Ser. No. 84,093 for Alcohol Soluble Basic Alusold under the trademark IRGASAN DP300 by Geigy Chemical Corporation.

minum Chlorides and Method of Making Same filed Oct. 26, 1970, by John L. Jones and Andrew M. Ru-

bino, assaying approximately 25.0 percent aluminum, 17.0 percent chloride, and 19.0 percent water was dissolved in 700 grams of ethyl alcohol (SDA,-40). To this alcoholic solution was added with constant agitation 3 3. Incubation of system 4. Final observation of M.l.C. The test samples are initially ball-milled to a particle size of about 5 microns. The ground sample is then disg f f hexachlorophene and 3 grams of trichlofocaf- 5 persed in sterilized, distilled water obtaining a homogeban1l1de.The resulting clear solution was evaporated at neous slurry. The test slurry is then added to nutrient IO IS mm Hg pressure and at 35C. to near constant broth previously inoculated with a specific concentra we ght to yield 300 grams of product. The homogeneity tion of test organism. The sample-broth system is then of the product was ver1f1ed by separately analyzlng varincubated at 35C for at least 24-30 hours for bacteria lous allquots of the product. The product contained 24 (for fungi, incubation is conducted at room temperapercent aluminum, 16 percent chloride, 19 percent wature for approximately 3 days), and then observations ter, 1 percent hexachlorophene and 1 percent triare made for indications of microbial life. The miniorocarbanlllde. mum concentration of test sample necessary for com- The utility of the present invention has been demon plete lnhlbltlon of the organism represents the reported strated by comparing the antimicrobial activity of the f synergistic combinations with the activity of the indi- Data for vaflous representatwe bdctefla and are vidual constituents or parent compounds of the system. gwen i Ig f g for Slmple admlxure These tests were carried out using standard broth diluso a e e e e 6 Systems represent t 056 tion techniques employing either nutrient broth orvnu- 20 dned from 9 anhyqrqus gi etha' triem agar The procedure employed in the tube dilw nol. The variance in relative antimicrobial activity per tion method to determine the minimum inhibition'congwen a le P Orgamsm m be accofmtable by the centration for a complete inhibition of test organisms F mdvmhtyfor a gf f (bacteria and fungi) by the antimicrobial test sample l fi y as a f gfi O i lfig r g may be broadly outlined as follows: t QPeratOl-S S l tee F', e e picts mlmmum concentrations of antimicrobial agent Test sample PQ for a complete inhibition using organisms which were 2. Test sample addition to nutrlent broth a" readily availaue (ATCC) culture types TABLE ll Minimum Inhibition Concentration in ppm BACTERIA FUNGl STAPH. TR. PS. PROT. STAPH. EPI- C. P. MENTA- COMPOUNDS & PARENTS E. COLI AERU- VULGARIS AUREUS DER- ALBICANS OVALE GRO- GINOSA MIDIS PHYTES 5/6 Basic Aluminum Chloride 6,000 1,500 6,000 2.000 2,000 2.000 5/6 Basic Aluminum Chloride 10,000 10,000 10,000 10,000 10,000 10,000 10,000 10,000 s/o Basic Aluminum Bromide 2,000 2,000 2,000 2,000 2,000 2,000 5/6 Basic Aluminum Iodide 700 900 500 I00 100 l,000 l,000 l,000 Hexachlorophene 80 l ,000 800 6 5 I ,000 I ,000 1,000 Hexachlorophene 100 10,000 1,000 100-10 100 10,000 1,000 1,000 Hexachlorophene 1 ,000 400 10 1 l 200 1,500 1,000 3,4,4'-Trichl0rocarbanilide 2,000 2,000 I00 2,000 -600 2,000 TCC 10 10,000 10,000 10 10 10,000 10,000 10,000 TCC 1 ,000 10,000 300 100 100 1,000 1 ,000 1,000 TCC 2,000 2,000 2,000 6 0.2 l,000 l,000 1 5/6 Basic Aluminum Chloride 800 20 1 1 20 I0 60 [0% TCC-l 0% Hexachlorophene e 2 5/6 Basic Aluminum Chloride 200 50 5 l l 10 20 I00 5% TCC-5% Hexachlorophene 3 5/6 Basic Aluminum Chloride 100 40 15 l l 20 20 500 10% TCC-20% Hexachlorophene 4 5/6 Basic Aluminum Chloride I20 40 I5 I l 30 30 20% TCC-10% Hexachlorophene 5 5/6 Basic Aluminum Chloride 300 60 l5 1 l 30 40 80 l% TCC-10% Hexachlorophene 6 5/6 Basic Aluminum Chloride -1,000 500 550 3 3 l,000

l% TCC-1% Hexzlchlorophene 7 5/6 Basic Aluminum Chloride l,000 300 400 50 30 I20 80 1% TCC-1% Hexachlorophene 8 5/0 Basic Aluminum Chloride 1,000 500 300 1 2 s00 40 l,000

l% T(C-l% Hcxachlorophene (spray dried from Ale.) 9 5/(1 Basic Aluminum Bromide -l,000 400 800 3 3 800 90 90 1% TCC-Wr- Hcxachlorophene it) 5/6 Basic Aluminum Iodide l,000 500 800 2 2 500 90 120 1% TCC-I% Hexachlorophene ll 5/6 Basic Aluminum Chloride 900 600 700 l l 2 2 2 10% TCC l0/r Hexachlorophene (admixture) 12 5/o Basic Aluminum Chloride 900 500 600 2 2 l,000 90 120 1% TCC-1% Hexachlorophene (admixture) l3 S/6 Basic Aluminum Chloride l,000 500 600 40 30 500 100 l7r- TCC-1% Hexachlorophene (admixture) l4 5/0 Basic Aluminum Chloride 1,000 800 800 1 1 -1,000 -400 -800 l7r TCC-l/r Hexachlorophene (admixture) l5 5/6 Basic Aluminum Chloride 500 900 20 l 1 -1,000 30 e 100 l'Yr TCC-1% Hcxachlorophene (admixture) As may be readily seen from a consideration of the results set forth in Table II above, the advantages of the novel tri-component composition are numerous. Such compositions exhibit broad spectrum antimicrobial activity against both Gram-negative and Gram-positive bacteria as well as against resident skin bacteria, dermatophytes, yeasts and various fungi. In addition, because of the low concentration of the halogenated bisphenol in the present antimicrobial compositions, the inherent limitations associated with the use of bisphenols such as hexachlorophene are reduced substantially. Moreover, since the basic aluminum halide constitutes at least 70 weight percent of the tri-component system, the inherent astringent and healing characteristics associated with such aluminum salts enhances the topical usage of the new composition. Thus, the present invention provides topically employable ingredients for creams, lotions, ointments, powders and the like where germicidal activity is required along with astringency and healing characteristics.

Results of tests with additional organisms run against an antimicrobial composition consisting essentially of 98 percent by weight of Al (OH) C1 x H 0, 1 percent by weight of trichlorocarbanilide (TCC) and 1 percent by weight of hexachlorophene ((1-1 1) are presented in 2 TABLE 111 Heart infusion medium Additional results illustrating the broad spectrum activity against both bacteria and fungi of the synergistic combination consisting essentially of in the range of from to 99.5 percent by weight of a basic aluminum halide, in the range of from 0.25 to 20 percent by weight of 2,4,4-trichloro-2-hydroxydiphenyl ether (IRGASAN DP300) and in the range of from 0.25 to 20 percent by weight of trichlorocarbanilide (TCC),

Table III. are set forth in Table IV.

TABLE IV Minimum lnhibition Concentration in ppm BACTERIA FUNGI STAPH. TR. E. PS. PROT. STAPH. EPI- C. P. MENTA- COMPOUNDS & PARENTS COL] AERU- VULGARIS AUREUS DER- ALBICANS OVALE GRO- GINOSA MIDIS PHYTES lrgasan DP300 or 0.1 2,000 0.05 200 200 200 2.4,4'-trichloro'2'-hydroxydiphenyl ether Ditto 300 -1.000 -1.000 2 2 g 500 800 800 Polyhalocarbanilide (TCC) 2,000 2,000 2,000 10-1 10-1 1,000 1.000 10-1 'AlCl, 6H,0 500 320 180 100 100 -1,000 1,000 1.000 A Basic Aluminum Chloride 500 500 700 100 100 800 1.000 1,000 Basic Aluminum Chloride 500 800 700 300 ;,ggg -;,ggg Aluminum Chlorh droxide 2,000 1,500 2,000 2, 00 Aluminum Chlorhydroxide 1.000 -1,000 -800 80 -100 600 1,000 1.000 (freeze dried) 1 98% A; Basic-Aluminum 400 400 50 l 2 1,000 1,000 -1,000

Chloride, 1% lrgasan DP300, 1% TCC 2 98% Basic Aluminum 400 500 20 1 2 900 900 700.

Chloride, I t 1% lrgasan DPJOO, 1% TCC 3 98% Aluminum Chloride. 500 320 30 2 6 900 900 700 1% lrgasan DP300. 1% TCC 4 98% Aluminum Chlorhydroxide, 100 1,00() 180 0.2 0.2 200 450 1 ,000

1.33% lrgasan DP300,,0.67% TCC 5 99% Aluminum Chlorhydroxide, 70 650 15 0.2 1 600 600 1,000

0.5% 1r asan DP300, 0.5% TCC- t 6 99.5% filuminum Chlorhydroxide 300 15 1,000 1 1 -800 900 900 0.25% lrgasan DP300. 0.25% TCC v 7 98% Aluminum Chlorhydroxide. 300 320 320 1 1 700 40 1% lrgasan DP300, 1% TCC 8 98% Aluminum Chlorhydroxide, 300 550 320 6 5 -1.000 280 -1,000

1% lrgasan DP300. 1% TCC 9 98% Freeze Dried Aluminum 800 800 20 l 2 400 500 700 Chlorhydroxide, 1% lrgasan DP300, 1% TCC 10 80% Aluminum Chlorhydroxide, 750 -1.000 10 8 1.000 800 -1,000

10% lrgasan DP300. 10% TCC 11 70% Aluminum Chlorhydroxide, 40 500 450 10 10 500 1,000 l,000

10% lrgasan DP300, 20% TCC 12 70% Aluminum Chlorhydroxode. 250 500 650 6 6 900 450 750 20% lrgasun DP300. 10% TCC 13 98% S/fi Basic Aluminum Bromide. 20 1,000 10 1 1 600 500 1,000

1% lrgasun DP300, 1% TCC 14 98% 5]) Basic Aluminum Iodide, 40 l,000 30 4 20 600 320 500 1% lrgusan DP300, 1% TCC 15 98% Aluminum Chlorhydroxide. l0 1.()00 30 1 1 500 300 320 1% lrgasan DP300. 1% TCC (admixture) 16 98% Aluminum Chlorhydroxide 10 900 20 1' 1 300 240 1% lrgasan DP300. 1% TCC ludmixture) Additional results, illustrating synergistic activity 7 with various basic aluminum chlorides combined with hexachlorophene (G11) and trichlorocarbanilide (TCC) are shown in Table V.

TABLE V Minimum Inhibition Concentration in ppm BACTERIA FUNGl 'IR. PS. I-ROT. STAPH. STAPH. C. P. MENTA- COMPOUNDS & PARENTS E. COLI AERU- VULGARIS AUREUS EPIDER- ALBICANS OVALE GRO- .GINOSA MIDIS PHY'I'ES 1 98% Aluminum Chloride, 320 90 100 2 2 90 600 1% G-ll, 1% TCC 2 98% A Basic Aluminum 1,000 150 150 2 1,000 280 280 Chloride, 1% G-l l, 1% TCC 3 98% Basic Aluminum 900 150 300 2 2 800 100 100 Chloride, 1% G1 1, 1% TCC 4 99% 5/6 Basic Aluminum 160 120 800 2 2 120 35 90 Chloride, 0.5% G-l 1, 05% TCC 5 99.5% 5/6 Basic Aluminum v750 90 800 5 4 320 60 500 Chloride. 0.25% G-l l, 0.25% TCC What is claimed is: 1. An antimicrobial composition consisting essentially of 1 i. from 70 to 99.5 percent by weight of an aluminum halide compound which can be represented by the formula:

where n is 0-5, where A is chlorine, bromine, iodine or a mixture thereof, and Q is selected from the group consisting of water a polyhydroxy compound having at least two carbon atoms each of which is linked to a hydroxy group and mixtures of water and said compound, and where the total amount of free andcoordinated constituent Q is in the range of from about to 40 percent by weight of the total weight ofthe basic aluminum halide compound, ii. from 0.25 to percent by weight ofa bactericidal agent selected from the group consisting of halogenated bisphenols and 2,4,4'-trichloro-2'- hydroxydiphenyl ether, and iii. from 0.25 to 20 percent by weight of 3,4,4-

trichlorocarbanilide or 3,3',4-trichlorocarbanilide. 2. An antimicrobial composition containing as its essential active ingredients a synergistic combination of l 70-995 weight percent of a basic aluminum halide compound of the formula Al (OH),. 6 nQ, where X is a halide selected from the group consisting of chlorine, bromine and iodine and mixtures thereof, and n is from 1 to 5, and Q is selected from the group consisting of water, a polyhydroxy compound having at least two carbon atoms each of which is linked to a hydroxy group and mixtures of water and said compound, (2) 0.25-20 weight percent of a bactericidal agent selected from the group consisting of polyhalobisphenols and 2,4,4'-trichloro-2'-hydroxydiphenyl ether and (3) 0.25-20 weight percent of 3,4,4'-trichlorocarbanilide or 3,3,'4-trichlorocarbanilide.

3. An antimicrobial composition consisting essentially of i. from 70 to 99.5 percent by weight ofa basic aluminum halide compound of the formula Al (0 )"X- tures of water and said compound,

ii. from 0.25 to 20 percent by weight of hexachloro phene, and,

iii. from 0.25 to 20 percent by weight of 3,4,4-

trichlorocarbanilide or 3,3 4-trichlorocarbanilide.

4. The composition of claim 3, wherein said basic aluminum halide compound'is five-sixths basic aluminum chloride. 1

5. The composition of claim 3, wherein said basic aluminum halide compound is five-sixths basic aluminum bromide. v l

6. The composition of claim 3, wherein said basic aluminum halide compound is five-sixths basic aluminum iodide. 1

7. The composition of claim 3, wherein saidbasic 40 aluminum halide. compound is one-third basicaluminum chloride.

8. The composition of claim 3, wherein said basic aluminum halide compound is two-thirds basicaluminum chloride. U u

9. The composition of claim 3, wherein said inorganic moiety is aluminum chloride.

10. An antimicrobial composition consisting essentially of 1. from 70 to 99.5 percent by weight ofa basic aluminum halide compound of the formula AI (OH),,X- s-nQ, where X is chlorine, bromine, iodine or a mixture thereof, n is from 1 to 5, and where Q is selected from the group consisting-of water, a polyhydroxy compound having at least two carbon atoms each of which is linked to a hydroxy groupand mixtures of water and said compound,

ii. from 0.25 to 20 percent by weight of 2,4,4-

trichloro-2'-hydroxydiphenyl ether, and

iii. from 0.25 to 20 percent by weight of 3,4,4-

trichlorocarbanilide or 3,3',4-trichlorocarbanilide.

11. The composition of claim 10, wherein said basic aluminum halide compound is five-sixths basic aluminum chloride.

12. The compositionof claim 10, wherein said basic aluminum halide compound is basic aluminum bromide.

13. The composition of claim 10, wherein said basic 15. The composition of claim 10, wherein said basic aluminum halide compound is basic aluminum iodide. aluminum halide compound is two-thirds basic alumi- 14. The composition of claim 10, wherein said basic chlondealuminum halide compound is one-third basic alumicomposltlQn of Clalm em said inornum chloride gamc moiety 18 aluminum chloride. 

2. An antimicrobial composition containing as its essential active ingredients a synergistic combination of (1) 70-99.5 weight percent of a basic aluminum halide compound of the formula Al2(OH)nX6 nQ, where X is a halide selected from the group consisting of chlorine, bromine and iodine and mixtures thereof, and n is from 1 to 5, and Q is selected from the group consisting of water, a polyhydroxy compound having at least two carbon atoms each of which is linked to a hydroxy group and mixtures of water and said compound, (2) 0.25-20 weight percent of a bactericidal agent selected from the group consisting of polyhalobisphenols and 2,4,4''-trichloro-2''-hydroxydiphenyl ether and (3) 0.25-20 weight percent of 3,4,4''-trichlorocarbanilide or 3,3,''4-trichlorocarbanilide.
 3. An antimicrobial composition consisting essentially of i. from 70 to 99.5 percent by weight of a basic aluminum halide compound of the formula Al2(OH)nX6 nQ, where X is chlorine, bromine, iodine or a mixture thereof, and n is from 1 to 5, and Q is selected from the group consisting of water, a polyhydroxy compound having at least two carbon atoms each of which is linked to a hydroxy group and mixtures of water and said compound, ii. from 0.25 to 20 percent by weight of hexachlorophene, and, iii. from 0.25 to 20 percent by weight of 3,4,4''-trichlorocarbanilide or 3,3'', 4-trichlorocarbanilide.
 4. The composition of claim 3, wherein said basic aluminum halide compound is five-sixths basic aluminum chloride.
 5. The composition of claim 3, wherein said basic aluminum halide compound is five-sixths basic aluminum bromide.
 6. The composition of claim 3, wherein said basic aluminum halide compound is five-sixths basic aluminum iodide.
 7. The composition of claim 3, wherein said basic aluminum halide compound is one-Third basic aluminum chloride.
 8. The composition of claim 3, wherein said basic aluminum halide compound is two-thirds basic aluminum chloride.
 9. The composition of claim 3, wherein said inorganic moiety is aluminum chloride.
 10. An antimicrobial composition consisting essentially of i. from 70 to 99.5 percent by weight of a basic aluminum halide compound of the formula Al2(OH)nX6 nQ, where X is chlorine, bromine, iodine or a mixture thereof, n is from 1 to 5, and where Q is selected from the group consisting of water, a polyhydroxy compound having at least two carbon atoms each of which is linked to a hydroxy group and mixtures of water and said compound, ii. from 0.25 to 20 percent by weight of 2,4,4''-trichloro-2''-hydroxydiphenyl ether, and iii. from 0.25 to 20 percent by weight of 3,4,4'' -trichlorocarbanilide or 3,3'',4-trichlorocarbanilide.
 11. The composition of claim 10, wherein said basic aluminum halide compound is five-sixths basic aluminum chloride.
 12. The composition of claim 10, wherein said basic aluminum halide compound is basic aluminum bromide.
 13. The composition of claim 10, wherein said basic aluminum halide compound is basic aluminum iodide.
 14. The composition of claim 10, wherein said basic aluminum halide compound is one-third basic aluminum chloride.
 15. The composition of claim 10, wherein said basic aluminum halide compound is two-third basic aluminum chloride.
 16. The composition of claim 10, wherein said inorganic moiety is aluminum chloride. 